Judit Daroczy The Dermal Lymphatic Capillaries With 174 Figures Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Dr. Judit Daroczy Kallai Eva Hospital of State's Hospital Stephan Kun n.4 1081 Budapest, Hungary Library of Congress Cataloging-in-Publication Data Daroczy, Judit. The dennallymphatic capillaries. Bibliography: p. Includes index.!. Skin - Lymphatics - Ultrastructure. I. Title. [DNLM: 1. Lymphatic System. WH 700 D224d] QM197.D37 1988 611'.4288-22421 ISBN-13: 978-3-642-73482-3 e-ISBN-13 978-3-642-73480-9 DOl 10.1007/978-3-642-73480-9 This work is subject to copyright. All rights are reserved, whether the whole or pan of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1988 Softcover reprint of the hardcover I 5t edition 1988 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Typesetting: Appl, Wemding 2127/3145-543210 Printed on acid-free paper Preface The importance of the lymphatic system has been known for a long time. It was therefore surprising to learn that the status of dermal lymphatics, under both normal and pathological conditions of man, had been largely neglected to date, particularly with respect to their ultrastructure. Moreover, the existing informa tion is incomplete, relating only to narrow segments of the skin, and it is con troversial. This monograph represents an effort to overcome some of the existing defi ciencies in the area of the structure (with emphasis on ultrastructure) of lym phatic capillaries. It is an account of our experience in the evaluation of dermal lymphatics in normal, edematous, and some other pathological conditions in man and in experimental animals. It is hoped that this information will prove useful for other investigators as a basis for evaluation of the structural and functional status of dermal lymphatics under a wide variety of pathological conditions. To the best of my knowledge, much of the information on the ultrastructure of the dermal lymphatics pre sented herein is new. This work would not have been possible without the inspiration of Prof. Dr. I.ANTON-LAMPRECHT, Head of the Institute for Ultrastructure Research of the Skin, Department of Dermatology of the University of Heidelberg, Federal Republic of Germany. I gratefully acknowledge the generous support of the Alexander von Hum boldt Foundation of Germany, which enabled me to carry out a major portion of the work upon which the monograph was based, in Heidelberg. Budapest, August 1988 Dr. JUOIT DAROCZY Table of Contents Materials and Methods 1 The Lymphatic Tree . 2 1.1 Lymphatic Trunk 2 1.2 Lymphatic Collecting Vessels 2 1.3 Lymphatic Capillaries. . . . . 2 2 How to Demonstrate Lymphatic Capillaries . 4 3 How to Identify Lymphatic Capillaries ... 5 4 Morphological Features of the Dermal Lymphatic Capillary 18 4.1 Pericapillary Connective Tissue ....... . 18 4.1.1 Basal Lamina ............. . 18 4.1.2 Endothelial Cytoplasmic Pseudopodia 18 4.1.3 Connective Tissue Microfilaments ... 18 4.1.4 Attachment Plates Along the Capillary Wall 19 4.1.5 Elastic Fibers . 19 4.1.6 Collagen Fibers ...... . 20 4.2 Endothelial Cells ......... . 20 4.2.1 Cytoplasmic Microfilaments 20 4.2.2 Microtubules ..... 20 4.2.3 Multivesicular Bodies. 21 4.2.4 Golgi Apparatus 21 4.2.5 Centrioles ...... . 21 4.2.6 Mitochondria .... . 21 4.2.7 Endoplasmic Reticulum 21 4.2.8 Ribosomes .. . 21 4.2.9 Cilia ..... . 21 4.2.10 Lipid Droplets . 21 4.2.11 Vesicles ... . 21 4.2.12 Lysosomes .. . 22 4.2.13 Dense Granules 22 4.2.14 Tubuloreticular and Crystalloid Inclusions 22 4.2.15 Nucleus 22 4.3 Innervation ...... . 22 5 The Lymphatic Valve System 46 5.1 Structure of the Valves . 46 5.1.1 Connective Tissue 46 5.1.2 Basal Lamina . . 46 5.1.3 Endothelial Cells . 46 VIII Table of Contents 5.2 Main Forms of the Lymphatic Valves 47 5.2.1 Joining Valves . . . 47 5.2.2 Segment Valves . . 47 5.2.3 Unicellular Valves. 48 5.2.4 Bunch Valves 48 5.3 Inlet Valves . . . . . . . . 49 6 Lymphaticovenous Anastomoses 76 7 Lymph Formation and Lymph Flow 77 8 Function of the Dermal Lymphatic Capillaries 80 8.1 Functional Morphology 80 8.2 Manner of Function ............ 81 9 The Role of Interstitial Proteolysis and Macrophages . 84 10 Pharmacology of the Dermal Lymphatic Capillaries 85 11 Inflammatory Conditions . . . . . . . . . . . . . . . 87 11.1 Morphological Changes of the Dermal Lymphatic Capillaries During Inflammation 87 11.2 Regeneration of the Lymphatic Capillaries . 87 11.3 Cellular Components in the Capillary Lumen and in the Pericapillary Space. . . . . . . . . 87 11.4 Role of the Lymphatic Capillaries in the Development of Cellularlmmunity . . . . . . . . . . . . . . . . . . 89 12 Mechanism of Transport Through the Lymphatic Capillary Wall 100 13 Insufficiency of Lymph Flow . . . . . . . . . . . . . . . . 101 13.1 Safety-Valve Function of Lymph Flow. . . . . . . . 101 13.2 Dynamic Insufficiency (High Lymph-Flow Failure) . 101 13.3 Mechanical Insufficiency (Low Lymph-Flow Failure) . 101 13.4 Safety-Valve Insufficiency. 101 14 Forms of Lymphedema . . . . . 102 14.1 Classification of Lymphostatic Edema 102 14.2 Clinical and Morphological Stages of Lymphostatic Edema 102 14.2.1 Latent Edema . . . . . . . . . 102 14.2.2 Manifest Edema (Reversible) . 103 14.2.3 Manifest Edema (Irreversible) 103 14.2.4 Elephantiasis. . . . . . . . 103 14.3 Inflammatory Skin Conditions Leading to Chronic Lymphedema 103 14.3.1 Usual Forms. . . . . . . . 103 14.3.2 Rare Forms ....... . 104 14.4 Diagnosis of Lymphostatic Edema 104 14.5 Histological and Electron-Microscopical Features of Lymphostatic Edema . . . . . . . . . . . . . . . 105 Table of Contents IX 15 Tumors of the Dermal Lymphatics 122 15.1 Lymphangioma . 122 15.1.1 Congenital ..... . 122 15.1.2 Acquired ...... . 123 15.2 Lymphangiosarcoma (Stewart-Treves Syndrome) 123 15.3 Pseudo Kaposi's Sarcoma. 124 15.4 Kaposi's Sarcoma ... 124 16 Lymphovascular Alterations in Different Syndromes Related to Dermatology 134 16.1 Melkersson-Rosenthal-Mischer Syndrome 134 16.2 Klippel-Trenaunay-Weber Syndrome 134 16.3 Nonne-Milroy-Meige Syndrome. 134 16.4 Noonan's Syndrome 134 16.5 Maffucci's Syndrome . 134 16.6 Yellow Nail Syndrome 134 17 Diabetes mellitus ..... . 135 18 Aged-Related Changes of Dermal Lymphatics 136 19 Lymphovascular Alterations in Selected Dermatological Diseases 137 19.1 Porphyria Cutanea Tarda . . 137 19.2 Hyalinosis Cutis et Mucosae 137 19.3 Lichen Amyloidosus . 13 7 20 Lymphangitis ........................ 144 20.1 Lymphostatic Lymphangitis and Edema . . . . . . . 144 20.2 Sclerosing Non-venereal Lymphangitis of the Penis. 144 20.3 Syphilis . . . . . . . . . . . . . . 144 20.4 Parasitic Lymphangitis ..... 144 20.5 Lymphangitis in Mucormycosis. 145 20.6 Lymphangitis due to Irritants. 145 20.7 Lymphangitis Carcinomatosa . 145 21 Treatment of Lymphostatic Edema . 148 21.1 Drug Therapy . . 148 21.2 Physical Therapy 148 21.3 Surgial Therapy 149 References . . 150 Subject Index 155 Materials and Methods Human Material. Normal and pathological skin Cleveland, Ohio) 20 min before being killed. of the forearm, lower leg, and back were stud Tissue samples from the upper and lower paws ied. The biopsies were taken from the follow were taken from the animals under ether ing disorders (under local anaesthesia): anesthesia. Blocks of skin from the upper and lymphedema, hyperkeratosis, atrophic skin le lower paws were fixed in KARNOVSKY'S fixative sions, ichthyosis vulgaris, pityriasis rubra pila (KARNOVSKY 1965) and postfixed in OS04 with ris, toxicoderma, lymphangioma circumscrip lanthanum according to SHEA (1971). The par tum, pseudo-Kaposi's sarcoma, Kaposi's sarco affin embedded materials were stained with he ma, porphyria cutanea tarda, hyalinosis cutis et matoxylin and eosin, orcein, GOMORI'S silver mucosae, lichen amyloidosus, lymphangitis impregnation, and WEIGERT'S resorcin-fuchsin carcinomatosa. staining. The samples for electron microscopic Experimental Material. Canine: Male and studies were fixed by immersion using KAR female canines weighing 15-25 kg were used NOVSKY'S fixative and postfixed with OS04 for this study. Lymphedema was produced by (DAROCZY and HUTTNER 1978). The tissues the ligation of the lymphatic trunk in the femo were treated for 2 h with uranyl acetate en bloc ral region (SOLTI 1986). Skin biopsies were tak and embedded in Epon. The semithin, tolui en from the normal hind limbs and from the dine-blue stained sections were reviewed by operated extremities of the animals after light microscopy. The thin sections were cut 10-14 days they were operated. Rat: Wistar with Reichert Vm02 ultrotome and examined rats weighing 150-200 g were injected i. v. with either unstained or following uranyl acetate 50 gl100 g body weight of native ferritin (dia and lead citrate staining with JEM 7A and lysed, Nutritional Biochemicals Corporation, Philips EM-600 microscopes. 2 1 The Lymphatic Tree The phylogenesis and comparative anatomy is prominent along the wall segments between are described for the large lymphatic vessels the valves. The elastic fibers do not form an and trunks (TONDGRY and KLBIK 1972). The elastic membrane, but rather a loose network lymphatic tree (human) can be grouped into accompanied by fibroblasts in the tunica ad three categories. ventitia (OEHMKE 1968; LEAK 1972 a). Unmyel inated nerve bundles can be present. The col lecting lymphatic vessels contain valves and 1.1 Lymphatic Trunk they have a well-developed basal lamina. The endothelial junctions are tightly closed; thus, large molecules and cells can not escape from The lymphatic trunk represents the thoracic the vessels but water and small molecules may duct and empties into the great veins of the migrate outward. neck. The vessel contains valves and the wall consists of three distinct tunics: (a) the tunica mtIma, compnsmg endothelial layer sur rounded by basal lamina, (b) the tunica media, 1.3 Lymphatic Capillaries consisting of alternating layers of smooth mus cle cells and collagen and elastic fibers, and (c) The smallest lymphatic vessels have been the tunica adventitia, composed of collagen termed "terminal lymphatics", "smalllymphat and elastic fibers intermingled with fibroblasts, ics", or "initial lymphatics". The different ter in addition to nerve bundles and small blood minologies are misleading; like the small blood vessels. vessels they are classified as capillaries. They contain valves, and the permeable wall consists of endothelial cells. The presence of endotheli 1.2 Lymphatic Collecting Vessels al gaps is common, and a continuous basal lamina is lacking. In the perivascular intersti The lymphatic capillaries empty into the lym tium the elastic fibers are intermingled with phatic collecting vessels. The collecting vessels collagen fibers and with the micro filaments are punctured with lymph nodes. They lie in running directly to the abluminal membrane of the mid and deep dermis, especially at the junc the capillary endothelial cells. tion of the dermis with the subcutaneous tissue The lymphatic plexus begins in the dermis and in the septa of fat lobules. The form of as blind tubes in the dermal papillae; these join their luminal cross sections depends on the with neighboring capillaries to form the super phase of their activity. The vessels can be oval, ficial lymphatic plexus. The deep lymphatic round, cruciform, or star-shaped. plexus is composed of lymphatics of varying The collecting vessels have three wall lay caliber, which are situated in the deeper layers ers: beneath the endothelial tunica intima the of the dermis (ZSDANOV 1952). smooth muscle cells create the tunica media. PFLEGER (1964 a) described postcapillary The muscle cells are intermingled with collagen lymphatics which were situated at the cutis and elastic fibers. At the basis region of the subcutis boundary. In their wall, smooth mus valves the smooth muscle layer is lacking, but it cle cells could be demonstrated. Lymphatic Capillaries 3 The term ''dermal lymphatic capillary" repre (eASLEy-SMITH and SIMS 1976). The lymphatic sents a lymph vessel lacking continuous basal lumen contains flocculent material which ap lamina and smooth muscle cells in its wall. pears medium dense under the electron micro The term "prelymphatics" represents the scope and it is interpreted as being protein-rich path of least resistance through the connective lymph. This flocculent material is observed in tissue directed toward the lymphatics. They are the adjacent perilymphatic areas as well. preformed paths in the vicinity of lymphatics